Bis-Met histones

Abstract

The present invention provides a nucleic acid molecule which encodes a polypeptide consisting of two methionine residues as the first and second N-terminal amino acid residues linked via a peptide bond to a mature eukaryotic histone. The present invention furthermore relates to a vector containing said nucleic acid molecule, a host transformed with said vector, polypeptides encoded by the nucleic acid molecule and pharmaceutical and diagnostic compositions. The present invention also relates to the use of the nucleic acid molecule, vectors, hosts and the polypeptide of the invention for the preparation of a composition for the treatment of diseases. Furthermore, the present invention relates to a method of testing for the presence of the nucleic acid molecule or the polypeptide in a sample and to a kit.

The invention claimed is: 
     
       1. A bis-met histone polypeptide comprising two methionine residues as first and second N-terminal amino acid residues linked via a peptide bond to a mature eukaryotic H1 histone. 
     
     
       2. The bis-met histone polypeptide of  claim 1 , wherein the mature eukaryotic H1 histone is a histone H1.0, a histone H1.1, a histone H1.2, a histone H1.3, a histone H1.4, a histone H1.5 or a histone H1t. 
     
     
       3. The bis-met histone polypeptide of  claim 1 , wherein an amino acid sequence including the second N-terminal amino acid residue, the peptide bond and the mature eukaryotic H1 histone is SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11 or SEQ ID NO: 13. 
     
     
       4. The bis-met histone polypeptide of  claim 1 , wherein an amino acid sequence including the second N-terminal amino acid residue, the peptide bond and the mature eukaryotic H1 histone is one having at least 85% sequence identity to SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11 or SEQ ID NO: 13 and retaining at least 20% of its biological activity. 
     
     
       5. The bis-met histone polypeptide of  claim 4 , wherein the amino acid sequence retains at least 50% of its biological activity. 
     
     
       6. The bis-met histone polypeptide of  claim 5 , wherein the amino acid sequence retains at least 75% of its biological activity. 
     
     
       7. The bis-met histone polypeptide of  claim 6 , wherein the amino acid sequence retains at least 80% of its biological activity. 
     
     
       8. The bis-met histone polypeptide of  claim 7 , wherein the amino acid sequence retains at least 85% of its biological activity. 
     
     
       9. The bis-met histone polypeptide of  claim 8 , wherein the amino acid sequence retains at least 90% of its biological activity. 
     
     
       10. The bis-met histone polypeptide of  claim 9 , wherein the amino acid sequence retains at least 95% of its biological activity. 
     
     
       11. The bis-met histone polypeptide of  claim 4 , wherein the amino acid sequence is one having at least 90% sequence identity to SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11 or SEQ ID NO: 13. 
     
     
       12. The bis-met histone polypeptide of  claim 11 , wherein the amino acid sequence is one having at least 95% sequence identity to SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11 or SEQ ID NO: 13. 
     
     
       13. The bis-met histone polypeptide of  claim 1  which is SEQ ID NO: 3. 
     
     
       14. A composition comprising the bis-met histone polypeptide of  claim 1  and optionally comprising a pharmaceutically acceptable carrier and/or a diluent. 
     
     
       15. The composition of  claim 14  further comprising a mature eukaryotic histone. 
     
     
       16. The composition of  claim 15 , wherein the mature eukaryotic histone is a histone H1 or a histone H2A. 
     
     
       17. The composition of  claim 14 , wherein the bis-met histone polypeptide comprises the amino acid sequence of SEQ ID NO: 3. 
     
     
       18. The composition of  claim 17 , wherein the bis-met histone polypeptide consists essentially of the amino acid sequence of SEQ ID NO: 3. 
     
     
       19. The composition of  claim 18 , wherein the bis-met histone polypeptide has the amino acid sequence of SEQ ID NO: 3. 
     
     
       20. A method of treating a leukemia, the method comprising administering a composition of  claim 14  to an individual in need thereof, wherein the disease is a leukemia. 
     
     
       21. The method of  claim 20 , wherein the leukemia is acute myeloic leukemia.